狂犬病灭活疫苗免疫佐剂的比较试验

本文利用反向遗传操作系统拯救出狂犬病病毒的携带双G基因的HEP-dG株,选用铝佐剂、蜂胶和油乳剂制成3种狂犬病灭活疫苗,进行小鼠免疫试验.试验表明,油乳剂和蜂胶佐剂狂犬病灭活疫苗免疫组效价较高.蜂胶狂犬病灭活疫苗二次免疫产生的抗体水平明显高于首免,油乳剂狂犬病灭活疫苗首免抗体水平与蜂胶狂犬病灭活疫苗二免产生的抗体水平相当.携带双G基因的HEP-dG株具有良好的免疫原性,油乳剂是作为该狂犬病毒株的最适佐剂.     

Protective efficacy of commercial inactivated Newcastle disease virus vaccines in chickens against a recent Korean epizootic strain

Despite the intensive vaccination policy that has been put in place to control Newcastle disease virus (NDV), the recent emergence of NDV genotype VII strains in Korea has led to significant economic losses in the poultry industry. We assessed the ability of inactivated, oil-emulsion vaccines derived from La Sota or Ulster 2C NDV strains to protect chickens from challenge with Kr-005/00, which is a recently isolated Korean epizootic genotype VII strain. Six-week-old SPF chickens were vaccinated once and challenged three weeks later via the eye drop/intranasal route. All vaccinated birds were fully protected from disease, regardless of the vaccine strains used. All vaccinated and challenged groups showed significant sero-conversion 14 days after challenge. However, some vaccinated birds, despite being protected from disease, shed the challenge virus from their oro-pharynx and cloaca, albeit at significantly lower titers than the unvaccinated challenged control birds. The virological, serological, and epidemiological significance of our observations with regard to NDV disease eradication is discussed.     

Effects of vaccine route and dosage on protection from rabies after intracerebral challenge in mice

OBJECTIVE: To evaluate the effect of various routes of administration and number of doses of 3 commercially produced rabies vaccines on serum antibody responses and protection in mice challenged by intracerebral injection with fixed-strain rabies virus. ANIMALS: 2,213 mice. PROCEDURE: Inactivated, adjuvanted rabies vaccines were administered to mice in either 2, 1, or 0 (control) doses via IP, IM, and SC routes, and mice were challenged intracerebrally with fixed-strain rabies virus. RESULTS: Vaccination route and dose number significantly influenced serum antibody responses and protection from rabies virus challenge, independent of vaccine strain origin and mouse strain, although mouse age significantly affected results. Extended challenge studies revealed that IM vaccination of mice resulted in the highest serum neutralizing antibody responses and protection levels equivalent to IP vaccination. Even multiple doses administered SC (a vaccination route used in dogs) resulted in poor serum anti-rabies neutralizing antibody responses in mice and were far less protective than other routes. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest possible improvements for the current rabies vaccine potency test in mice by using 1 dose, the IM route, and a delayed time of challenge. These modifications would more closely model vaccination practices in target species and yield more accurate information regarding primary immunogenicity of a vaccine.     

狂犬病灭活疫苗CVS-11株对牛的免疫效果

野生狐和貉狂犬病流行于新疆、内蒙古和黑龙江地区,是当地牛、羊和骆驼等家畜狂犬病的主要传染源。在国内尚无野生动物口服疫苗的前提下,对家畜进行狂犬病灭活疫苗接种,具有重要的公共卫生学意义。本研究利用国产犬用狂犬病灭活疫苗(CVS-11株)对牛进行了免疫效果和安全性评价。以不同剂量疫苗肌内注射免疫成年牛350头,通过比较免疫后狂犬病病毒中和抗体水平和持续期,确定犬用狂犬病灭活疫苗(CVS-11株)在牛的最佳免疫剂量为1次性注射2剂量疫苗,免疫持续期为1年。结果表明,犬用狂犬病灭活疫苗(CVS-11株)免疫牛时,具有较高的免疫原性和安全性,适用于牛等大型动物的狂犬病注射免疫。     

狂犬病弱毒SRV9对街毒暴露小鼠的治疗效果

为评估狂犬病弱毒SRV9对狂犬病街毒暴露小鼠的治疗效果,首先将SRV9通过脑内和肌肉接种3周龄ICR小鼠检测其安全性,然后应用狂犬病街毒接种小鼠,随后在暴露后不同时间用SRV9治疗,研究其保护率.结果显示,SRV9对3周龄ICR小鼠安全,在街毒暴露后1、2、3d,SRV9的保护率分别为70％、60％、30％,而相同暴露时间下单剂量灭活疫苗联合免疫球蛋白的保护率分别是30％、20％、10％.对应用SRV9治疗而成活小鼠的中和抗体检测,发现所有小鼠的抗体水平均达到0.5 IU以上,这些数据初步显示活弱毒SRV9具有用于暴露后治疗的潜力.     

Effect of thimerosal concentration on the efficacy of inactivated Newcastle disease oil-emulsion vaccines

Different quantities of the preservative thimerosal in inactivated Newcastle disease oil-emulsion vaccines were tested to determine the influence on the hemagglutination-inhibition (HI) response of broilers. The effect of thimerosal was measured in vaccines that had been stored for 1, 21, and 52 weeks; HI serology was conducted at 2, 4, and 6 weeks after vaccination. Mean HI titers 4 weeks after vaccination decreased at a significant rate (P less than or equal to 0.001) with increasing concentrations of thimerosal. HI titers 4 weeks after vaccination with 1-week-old vaccine were significantly (P less than or equal to 0.05) higher than those after vaccination with 52-week-old vaccine at all thimerosal concentrations tested. Titers were also significantly higher (P less than or equal to 0.05) after vaccination with 1-week-old vaccine than after vaccination with 21-week-old vaccine at all thimerosal concentrations below about 8.25 mg/ml of antigen. Thimerosal at the levels recommended in commercial vaccines does not significantly decrease vaccine efficacy.     

应用小白鼠代替鸡对禽霍乱蜂胶灭活疫苗进行效检的研究

为寻找其他有效的禽霍乱蜂胶灭活疫苗的效检方法,应用小白鼠代替本动物鸡对禽霍乱蜂胶灭活疫苗进行效检.结果表明,小白鼠免疫时体重15～18 g,疫苗免疫剂量0.3 mL/只,免疫10 d后攻毒,攻毒时体重20～25 g,攻毒剂量5～9 CFU/只时,可代替本动物鸡对禽霍乱蜂胶灭活疫苗进行效检,判定标准为免疫组8/10以上保护,对照组5/5死亡为合格.本效检方法可缩短检验期限7 d,降低检验成本,具有敏感、特异、客观、简便等特点.     

Comparison of antibody responses after vaccination with two inactivated rabies vaccines

Thirty laboratory dogs were randomly assigned to two groups (A and B) of 15 dogs and subcutaneously vaccinated with a single dose of one of two commercially available monovalent inactivated rabies vaccines: RABISIN (Merial, France) (group A) and NOBIVAC Rabies (Intervet International) (group B). Rabies antibodies were measured over a period of 4 months using the fluorescent antibody virus neutralization (FAVN) test. The two vaccines performed differently in terms of magnitude and persistence of rabies antibodies titers in dogs. Two weeks after vaccination, average rabies antibody titers peaked at 2.53 IU/mL (range, 0.17-13.77 IU/mL) and 1.26 IU/mL (range, 0.50-4.56 IU/mL) in groups A and B dogs, respectively. The average FAVN antibody titres against rabies on D28, D56, D84, D112 and D120 were significantly higher in group A than in group B. Although all dogs from group B serologically responded to vaccination, the proportion of dogs with antibody titres >or=0.5 IU/mL dropped significantly after D28 and was statistically significantly lower on D56, D84 and D112 compared to group A dogs. In conclusion, in the context of international trade, the choice of the vaccine and the timing of blood tests are critical factors in achieving successful serological test results after rabies vaccination. RABISIN induces high and sustained antibody titres against rabies, increasing the flexibility for the time of blood sampling after primo-vaccination.     

Vaccination of pigs against Aujeszky's disease by the intradermal route using live attenuated and inactivated virus vaccines

A study was undertaken of the protection induced by inactivated and live Aujeszky's disease virus vaccines. The vaccines were administered using a special device which, without the use of a needle, delivered the preparation intradermally. The trials were performed on 88 pigs which were vaccinated at the beginning of the fattening period both in experimental conditions and in pig herds. All the pigs were challenged at the end of the fattening period in isolation units. The results obtained were compared with those obtained using the same vaccines injected intramuscularly. It was shown that vaccination via the intradermal route induced good protection in the vaccinated animals and was similar to that conferred by live virus vaccine injected intramuscularly. The results, with the inactivated virus vaccine, were not so good when it was injected via the intradermal route. Studies with intradermal vaccination showed no local lesion or very small nodules strictly localized to the dermis. The results also confirmed that the effects of challenge exposure depended on the health status of animals prior to infection and show the necessity to use a synthetic value (delta G) to interpret the data and mainly to compare the results objectively. In fattening pigs this vaccination procedure is attractive because (i) less animal constraint is needed than would be for intramuscular injections, (ii) injection can be checked by the presence of a visible papula at the site of inoculation and, (iii) pigs can be vaccinated in the ham while they are feeding. Injection without a needle also contributes to avoiding bacterial contamination under practical farm conditions of vaccination.     

Evaluation of an inactivated rabies virus vaccine in domestic ferrets

Efficacy of an SC-administered commercial inactivated vaccine for prevention of rabies was evaluated in domestic ferrets. Ferret immunity was challenged by the IM inoculation of street rabies virus. All ferrets developed titers of rabies virus-neutralizing antibodies within 30 days of vaccination (geometric mean titer [GMT] = 154, n = 41) that were maintained for at least one year (GMT = 106, n = 36), compared with no seroconversion in controls (GMT less than 5, n = 39). Following rabies virus challenge inoculation, 89% (32/36) of vaccinated ferrets survived vs less than 6% (2/38) survival in control ferrets. These results demonstrate the protective efficacy of a commercial, inactivated rabies vaccine of at least one year's duration for domestic ferrets.     

Vaccination of pigs against Aujeszky's disease by the intradermal route using live attenuated and inactivated virus vaccines.

Inactivated and live Aujeszky's disease virus vaccines were administered intradermally using a special device without a needle. The 88 pigs were vaccinated at the beginning of the fattening period, both under experimental conditions and in commercial herds. All the pigs were challenged at the end of the fattening period in isolation units. The same vaccines were also injected intramuscularly. Vaccination by the intradermal route induced good protection, similar to that conferred with live virus vaccine injected intramuscularly. The inactivated virus vaccine was not as effective when it was injected by the intradermal route. In animals vaccinated intradermally, there were no local lesions in the meat, but very small nodules were found in the dermis; these do not affect carcass quality. The effects of challenge exposure depended on the initial health of the animals, and a synthetic value (delta G) was used to interpret the data. In fattening pigs, intradermal vaccination required less animal constraint than intramuscular injection; administration could be verified by the presence of a papule at the site of inoculation, and pigs could be vaccinated while they were feeding. Injection without a needle also helps avoid bacterial contamination under farm conditions.     

Protective efficacy of H5 inactivated vaccines in meat turkey poults after challenge with Egyptian variant highly pathogenic avian influenza H5N1 virus

In contrast to chickens, there is a paucity of information on the potency of H5 vaccines to protect turkeys against the highly pathogenic avian influenza (HPAI) H5N1 virus infections. In this study, 4 groups, 10 turkey poults each, were vaccinated at seven days old with one of H5N2 or H5N1 commercial vaccines or one of two prepared H5N1 vaccines from a local Egyptian variant HPAI H5N1 (EGYvar/H5N1) strain. At 35 days age, all vaccinated and 10 non vaccinated birds were challenged intranasal with 10(6) EID(50)/0.1 ml of EGYvar/H5N1. All vaccines used in this study were immunogenic in turkeys. There was no cross reaction between the commercial vaccines and the Egyptian variant H5N1 antigen as obtained by the hemagglutination inhibition test. Birds vaccinated with H5N2 vaccine were died, while other H5N1 vaccinated groups have had 20-40% mortality. The highest virus excretion was found in non-vaccinated infected and H5N2 vaccinated birds. Eleven peculiar amino acid substitutions in H5 protein of the variant strain were existed neither in the vaccine strains nor in the earliest H5N1 virus introduced into Egypt in 2006. In conclusion, single vaccination at seven days old is inadequate for protection of meat turkeys against variant HPAI H5N1 challenge and multi-dose vaccination at older age is recommended. For the foreseeable future, continuous evaluation of the current vaccines in H5N1 endemic countries in the face of virus evolution is a paramount challenge to mitigate the socio-economic impact of the virus.     

Efficacy of viable and inactivated Newcastle disease virus vaccines in turkeys

Market turkeys spray-vaccinated at 20 days of age with viable Newcastle disease virus (NDV) vaccine and challenged 7 weeks postvaccination failed to yield NDV by tracheal swabbing 4 days postchallenge but demonstrated serologic evidence of infection. Birds vaccinated subcutaneously with inactivated oil-emulsion (OE) NDV vaccine had virologic and serologic evidence of infection. Breeder hens vaccinated by spray with commercial La Sota vaccine at 19 weeks of age and revaccinated subcutaneously with OE vaccine at 32 weeks of age had an adequate level of resistance against a drop in egg production but demonstrated serologic evidence of infection when challenged with velogenic NDV at 38 weeks of age.     

重组禽流感病毒二价灭活疫苗对H5N1亚型7.2分支病毒的攻毒保护性研究

为有效防控2006年以来出现的H5亚型7.2分支禽流感病毒(AIV)引起的免疫鸡群高致病性禽流感(HPAI)的流行,我们构建了重组AIV Re-4疫苗株,研制出含有重组AIV Re-4株的H5亚型二价系列灭活疫苗,并在我国北方地区使用,有效地控制了其流行。2012年我国北方地区再次出现7.2分支病毒引起的HPAI疫情。为评估现有H5亚型二价系列灭活疫苗对该分支病毒的免疫保护效力,本研究首先通过SPF鸡进行免疫攻毒试验评估。结果表明,分别以每羽份(0.3 mL/只)的Re-5+Re-4株和Re-6+Re-4株重组AIV H5二价油乳剂灭活疫苗免疫SPF鸡,免疫3周后针对重组AIV Re-4株的HI抗体均达到8 log2以上;经鼻腔接种7.2分支AIV CK/NX/2/12株(100 LD50)攻毒后,免疫鸡均获得完全保护,即无任何临床症状和排毒现象,而对照组SPF鸡全部发病死亡。此外,以哈尔滨当地养殖场中免疫H5亚型AIV灭活疫苗的48只商品蛋鸡进行攻毒试验,结果显示,商品蛋鸡血清中针对重组AIV Re-4株HI抗体平均滴度为8.3 log2,采用相同方式攻毒后也获得完全保护。本研究结果表明,Re-5+Re-4株和Re-6+Re-4株重组AIV H5二价灭活疫苗均能够对H5亚型7.2分支病毒的攻击提供良好的免疫保护效果。     

Immunization of foxes by the intestinal route using an inactivated rabies vaccine.

Approximately 30% of foxes given two doses of an inactivated rabies antigen delivered directly into the intestinal tract developed an immune response as measured by rabies serum neutralizing antibodies. Seven of ten previously immunized foxes showed an anamnestic response following a booster dose of inactivated rabies antigen delivered to the intestinal lumen. Stomach and particularly intestinal contents were destructive to rabies antigen and virus. This effect could be partially neutralized in vitro by the addition of Questran and soybean trypsin inhibitor. Small enteric coated tablets fed to foxes in a hamburger bolus remained in the stomach for up to 13 hours and therefore would provide a poor vehicle for the delivery of antigen to the intestinal tract.     

Vaccination of cattle with live and inactivated rabies vaccines: a study of antibody response

The authors vaccinated 152 cattle divided into three groups against rabies. The first group received the ERA strain and the second group an inactivated vaccine. The third group received the inactivated vaccine on two occasions with an interval of 60 days between the two doses. Their antibody response was surveyed with the fluorescent foci-inhibition test carried out on blood samples collected during a 10-month period. All animals developed an almost identical antibody response. However, at the sixth and tenth months, there was a higher number of seropositive animals in the groups vaccinated with the killed vaccine.